Influence of heart rate and sympathetic stimulation on arrhythmogenic T wave alternans

We determined the temporal stability of T wave alternans (TWA) during const ant rate stimulation and the dependence of alternans on heart rate (HR) and beta-adrenergic stimulation. Although it is established that exercise can provoke microvolt-level TWA in patients at risk for reentrant ventricular a rrhythmias, the mechanisms underlying TWA in humans are not well understood . Specifically, the temporal stability of alternans at any given HR and the influence of HR vs. sympathetic activation on alternans remain unclear. TW A was measured during prolonged fixed-rate atrial pacing at multiple cycle lengths (CLs) in 10 subjects referred for electrophysiological testing and in 14 additional subjects in whom atrial pacing was performed at identical pacing CLs with and without isoproterenol. During constant CL stimulation, TWA amplitude oscillated significantly over time (typically by 10 mu V) in a quasiperiodic fashion with periodicity of similar to 2-3 min. Alternans a mplitude was strongly dependent on HR but not on adrenergic stimulation. Th ere was a patient-specific threshold HR over which alternans appeared. At h igher HR, alternans amplitude increased and oscillations were less prominen t. Adrenergic stimulation was required to produce TWA that was not already elicited by moderate elevation of HR in only 2 of 14 (14%) patients. In con clusion, TWA 1) fluctuates spontaneously over 2-3 min and 2) increases mono tonically with increased HR (without a major adrenergic contribution in mos t patients). These data suggest that increased HR rather than sympathetic a ctivation is responsible for arrhythmogenic microvolt-level TWA measured du ring exercise.